Intermittent resting of CAR T cells by preventing tonic signaling prevents and reverses exhaustion (from PxHere)

Persistent, antigen-independent signaling through chimeric antigen receptors (CAR)—tonic signaling—can lead to CAR T-cell exhaustion. Weber et al. show that the functional, transcriptional, and epigenetic hallmarks of exhaustion that occur in CAR T cells because of tonic signaling can be prevented and reversed by intermittent cessation of tonic signaling by either switching a drug-regulated CAR on and off or using the small molecule dasatinib to inhibit proximal CAR signaling. Intermittently rested CAR T cells improve tumor control and survival in xenograft models, highlighting the potential clinical applicability of the data.

Weber EW, …, Mackall CL. Science 2021 Apr 2;372:eaba1786.

Epigenetic immunoediting creates an immunosuppressive TME in GBM (from Nephron via Wikimedia Commons)

Glioblastoma multiforme (GBM) is refractory to immunotherapy, but knowledge of the immunosuppressive mechanisms at play in the tumor microenvironment (TME) is limited....

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